Cancer, vitamin supplements, and unexpected consequences

Warning: High dose supplementation of B-vitamins is associated with an increase in the risk of lung cancer.

Vitamin supplements have been successfully marketed for decades, despite the lack of good evidence that they are necessary or beneficial for the vast majority of people that take them. While frank deficiencies of vitamins are generally rare (you don’t see scurvy much anymore), dietary restrictions, pregnancy, and even socio-economic status may increase the possibility of a deficiency and an evidence-based recommendation to supplement. It’s more of an open question if supplementation in the absence of any clear medical need is advisable or necessary. As a pharmacist I’ve spent a lot of time over the years speaking with patients about vitamin supplementation. Many seem to take the view of vitamins as a reasonable “insurance policy” for their diet, and a net positive thing they can do to support healthy living. Early in my career, I viewed vitamin supplementation without any clear medical clear need as producing “expensive urine” for the user, but unlikely to cause much harm. But over the past 25 years, evidence has emerged to change my view. I am much more skeptical now of the net benefit of vitamin supplementation. That position is based on the results of multiple studies that have shown that vitamin supplementation is not always harmless – in some cases it appears to be harmful, and should be discouraged.

Many of the problems with vitamin supplementation have emerged when we have assumed that isolated vitamins are an appropriate or equivalent substitute for foods that contain those same vitamins. Compound this with the equally bad idea that more=better, and you have supplement doses much higher than would be consumed in diet alone. Antioxidants are the most representative example. The idea for antioxidants emerged from observations about oxidative stress and their contribution to illness and aging, and the hypothesis that antioxidant supplements could minimize these effects. Yet trials have failed to show that antioxidant supplements have the same effects as antioxidant-rich foods. Over time it became clear that beta-carotene supplements could raise your risk of cancer. Vitamin E supplements also appears to raise, rather than lower, prostate cancer risk. Steven Novella’s post from 2015 summarizes the evidence on vitamins and cancer risk, and provides the backdrop to the study I want to review today that illustrates the cautious, deliberate approach we should take to supplementation.

Studying the effect of B-vitamin supplementation

Any pharmacy that you walk through will likely have several shelves of different combinations of vitamins all touted with specific purposes. “Stresstabs” are a popular vitamin brand sold around the world that are essentially a multivitamin with added B vitamins. Presumably created based on some idea that stress depleted B-vitamins, or could be relieved with B-vitamins, Stresstabs were very popular in the local pharmacy where I worked where patients thought they could get a “quick fix” from the stress in their lives. There’s also B12 supplements which continue to be marketed as some kind of energy panacea despite the lack of any evidence they do anything useful if you’re not deficient.

The authors start out by noting that the results from previous studies of B-vitamins and lung cancer have been unclear, yet there have been hints of the risk of harm. The authors hypothesized that doses of B-vitamins in excess of the Recommended Daily Allowance (RDA) might be cancer-promoting through effects on the cellular environment. This analysis draws on data collected from the VITamins And Lifestyle cohort study, initiated in 2000 to study the association of vitamin supplements with cancer risk. Over 77,000 men and women aged 50-76 years living in Washington state were enrolled, with the objective of tracking cancer and deaths. As part of the study, participants reported their regular consumption of vitamins (individual products and multivitamins) over the prior 10 years. The 10-year average daily dose of vitamins B6, B9, and B12 were calculated, and participants were stratified by doses consumed, ranging from multivitamin-level-doses (small) to what would be considered high doses.

In addition to supplementation habits, dietary habits were assessed using standardized questionnaires, and multiple health-related risk factors (e.g., smoking history) were also collected.

Patients were followed for the incidence of lung cancer from baseline (2000-2002) through December 31, 2007. The incidence of cancer was determined through linkage to the SEER cancer registry. 808 cases of invasive lung cancer were identified in the cohort.

The statistical analysis is complex and used models to estimate hazard ratios and confidence intervals for the association between doses of B-vitamins and the risk of lung cancer. They tried to identify and control for as many confounders as possible (e.g., adjusting for smoking rates, or adjusting B-vitamin intake based on caloric intake).

The findings were pretty striking. Based on information collected when participants enrolled in the study, former use of individual supplements of vitamin B6 or B12 was associated with an increase in lung cancer risk in men, but not women. Compared to no supplementation, vitamin B6 increased the risk of lung cancer by 84%, and vitamin B12 was observed to more than double risk. Looking at the 10-year average daily dose, the increase in cancer risk was associated with the highest levels of supplementation: more that 20mg/day of B6 and more than 55mcg/day of B12. No association was found between folate (folic acid) and lung cancer risk. The trend was most significant in smokers. There were no beneficial effects of supplementation seen in any group.

Implications

This study gives fairly compelling evidence that consumption of high doses of vitamins B6 and B12 are associated with an increased lung cancer risk. This association was found in men only, and was stronger in smokers. No association was found in women, and no association was found with the consumption of B-vitamins in the low doses contained in multivitamins. The authors suggest that doses of B6 and B12 that are taken in excess of dietary requirements may be causing pro-cancer effects.

Key considerations

Perhaps not surprisingly, industry advocates have moved quickly to question or dismiss the findings (“Statistical chance” says one) and criticizing the coverage of the trial. But what’s arguably just as important as the elevated risk of lung cancer observed is the fact that there was no evidence found to suggest that B-vitamin supplementation offers any meaningful benefit, either.

Despite that marketing that vitamin-or-supplement-de-jour can prevent cancer or help you live longer/better, there is actually little evidence that any vitamin or mineral supplement has any meaningful or beneficial effects in the absence of a true deficiency. Vitamin supplementation remains exceptionally popular, and this new study should be considered in the context of other studies that have raised concerns that these products may be causing harm. Vitamin supplementation can be medically appropriate, but we should not view indiscriminate supplementation as a panacea or as harmless insurance against dietary deficiencies. And if we elect to take a vitamin supplement, isolated vitamin supplements may deliver the higher doses that appear to be associated with more risk. Probably the best advice that can come from studies like this is that we don’t fully understand the consequences of our vitamin supplement habit. Focusing on a healthy, balanced diet to meet our vitamin needs is the approach that appears to offer the best benefits and the fewest risks.